Cellular immune responses to tumor are considered important in the control of appearance and spread of cancer. Previous work in human bladder carcinoma has suggested that patients with this disease may have blood lymphocytes which exert cytotoxic effects on tumor cells in vitro and that the appearance of this reaction may in some way be correlated to the presence of tumor and the patient's immune response. Recent studies have suggested that a considerable amount of the controversy in the literature over these findings may be due to methodological differences. Therefore, further examination of the basic cytotoxic phenomenon in vitro is needed in order to clarify whether measurements of cell-mediated cytotoxicity are immunologically and clinically useful in man. Studies of antibody-dependent cell-mediated cytotoxicity to bladder tumor cells may be useful in clarifying the type of cytotoxic responses being observed. In addition, it appears to be of importance to measure general immunological competence and cellular immune reactivity of lymph nodes regional to bladder cancer as well as that of the blood leukocytes. Preliminary studies have shown that the ability of patients' leukocytes to act as stimulator cells in one way mixed leukocyte culture (MLC) may be depressed with tumor presence and return to normal with removal of tumor. The immunologic responsiveness of the regional lymph node cells decreases with advancing stage of disease, and the regional lymph nodes may exhibit decreased ability to stimulate in MLC and some possess an ability to suppress MLC reactions. These phenomenon appear to correlate with the histological evaluation of the reactivity of the regional lymph nodes. A retrospective study has shown a highly significant positive correlation of five year survival with a stimulated node pattern. Further analysis of these in vitro reactions with close clinical followup is necessary to determine the incidence, relevance to clinical stage, and mechanisms of action producing these reactions. Such studies have potential to add information relative to the clinical staging and/or prognosis of patients with carcinoma of the bladder.